Implementation of a joint protocol for the management of thyroid nodules with a cytological diagnosis of follicular lesion of undetermined significance: experience in one hospital.

BACKGROUND: Follicular lesion of undetermined significance (FLUS) was introduced for fine needle aspiration (FNA) cytology in which there is insufficient evidence to classify the lesion as follicular neoplasm/suspicious of follicular neoplasm or suspicious for malignancy. The recommended management was repeat FNA and correlation with clinical and radiological data. In 2009 we started a joint clinicopathological protocol to improve management of FLUS, recommending follow-up with repeat FNA at 6months. The aim of this study was to report on the audit of results of this protocol. METHODS: We reviewed the medical records of the patients with FLUS at a single hospital. Between 2007 and 2010 we found 135 cases with this diagnosis (3.6%). We only had long enough follow-up information for the 95 patients that were included in the present study. RESULTS: FLUS was diagnosed in 74 FNAs before protocol implementation (3.2%) and 61 FNAs after (4.2%), with follow-up of 46 and 49 patients, respectively. Before 2009, 38/46 (82.6%) patients had surgical excisions, compared with 32/49 (65.3%): a significant reduction of 17% in the number requiring surgery (P=0.05). We have also shown a reduction in the median time to surgery (11.9 versus 2.9 months). Despite the joint protocol, the FNA was only repeated in two patients. The histological diagnoses were similar in the two periods of time: 31.6% and 31.3% follicular adenomas; 13.1% and 3.1% (P=0.2) papillary carcinoma (follicular variant). CONCLUSIONS: Implementation of a joint protocol reduced the number of surgical operations in patients with FLUS but in most cases FNA was not repeated as recommended. Excision was justified in one-third of operated patients. Less than 15% of lesions were malignant, which is in accordance with previous reports in the literature.

Endogenous Developmental Cycle of the Human Coccidian Cyclospora cayetanensis.

Cyclospora cayetanensis is a coccidian parasite of humans of known and growing importance. However, we are surprisingly naïve as to our understanding of how to diagnose it and how it develops inside the human body. Here we provide details of the developmental stages of C. cayetanensis in the gallbladder of a 33-yr-old male with human immunodeficiency virus. The gallbladder was removed surgically in 2001 because of severe abdominal pain. For the present study, the archived paraffin block of gallbladder was processed for light microscopy and transmission electron microscopy (TEM). Histological sections were examined after staining with hematoxylin and eosin (HE) or using the periodic acid Schiff (PAS) reaction. Immature and mature asexual stages, gamonts, and oocysts were seen in epithelial cells, both in the superficial epithelium and in glands. The merozoites were present singly, in pairs, and 3 or more in a single parasitophorous vacuole in the host cytoplasm. Up to 6 nuclei were seen in immature schizonts without evidence of merozoite formation. Mature schizonts were 7.6 × 5.1 µm and contained up to 10, 3-4 µm long merozoites. Merozoites were 0.6 to 2.0 µm wide, and their shape varied from pear-shaped to slender. Merozoites were generally PAS-positive; however, some were intensely positive, some had only minute granules, while others were PAS-negative. The microgamonts (male) were 6.6 × 5.2 µm and contained fewer than 20 microgametes around a residual body. The microgametes were up to 2 µm long and were flagellated. Macrogamonts (female) contained distinctive eosinophilic wall-forming bodies that varied in size and were less than 1 µm in HE-stained sections. Macrogamonts were 5.8-6.5 × 5.3-6.5 µm. Oocysts in sections were unsporulated and had a diameter of 5.7-7.5 µm. The TEM examination confirmed the histologic findings. The DNA extracted from paraffin sections was confirmed as C. cayetanensis with real-time PCR. The detailed description of the life cycle stages of C. cayetanensis reported here in an immunosuppressed patient could facilitate histopathologic diagnosis of this parasite. We have shown that the parasite's development more closely resembles that of Cystoisospora than Eimeria and that the parasite has multiple nuclei per immature meront indicating schizogony, and we have undermined evidence for a Type II meront.

Role of Gait Speed, Strength, and Balance in Predicting Adverse Outcomes of Acutely Ill Older Outpatients.

AIM: To evaluate the ability of the Short Physical Performance Battery (SPPB) for predicting 1-year adverse outcomes of acutely ill older outpatients. METHODS: Prospective study with 512 acutely ill older outpatients (79.4±8.3 years, 63% female) in an acute care day hospital. The SPPB was administered at admission. Participants were classified as low (0-4 points), intermediate (5-8 points), or high (9-12 points) performance. Primary outcomes were new dependence in basic activities of daily living (ADL), hospitalization, and death at 1 year. Cox models tested whether the SPPB predicted outcomes after adjustment for sociodemographic factors, comorbidities and well-known geriatric conditions. We also estimated whether the chair-stand and balance tests improve the SPPB's ability to identify patients at high risk of adverse outcomes. RESULTS: Patients with intermediate or low SPPB performance were at higher risk of 1-year new ADL dependence (32% vs 13%: adjusted hazard ratio [aHR]=2.00; 95%CI=1.18-3.37; 58% vs 13%: aHR=3.40; 95%CI=2.00-5.85, respectively), hospitalization (43% vs 29%: aHR=1.56; 95%CI=1.04-2.33; 44% vs 29%: aHR=1.80; 95%CI=1.15-2.82), and death (18% vs 6%: aHR=2.54; 95%CI=1.17-5.53; 21% vs 6%: aHR=2.70; 95%CI=1.17-6.21). Use of all three components (versus gait speed alone) improved predictions of new ADL dependence (Harrell's C=0.73 vs 0.70;P=0.01), hospitalization (Harrell's C=0.60 vs 0.57;P=0.04), and death (Harrell's C=0.67 vs 0.62;P=0.04). CONCLUSIONS: The SPPB is as a powerful tool for identifying acutely ill older outpatients at high-risk of adverse outcomes. The combination of the three components of the SPPB resulted in better predictive performance than gait speed alone.

Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant treatment of early breast cancer: analysis of biological markers in a GEICAM phase II study.

INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.

The Negro River (Ancash-Peru): A unique case of water pollution, three environmental scenarios and an unresolved issue.

This paper is focused on the hydrogeochemical characterization of the Negro River along its course, as well as in the proposal of a functioning model for the contamination processes in order to establish potential cause-effect relationships between water quality, geology (ARD), mining activities (AMD) and the tectonic framework as transmission vector of acidity, metals and sulphates. The scenario shows a heavily-contaminated river compared to the unaffected regional background. By graphical and statistical treatments of physico-chemical data of Negro River and the unaffected values of regional background and other AMD/ARD representative rivers' it is possible to conclude that Antamina Mine, is not the cause of the Negro River contamination, without the need of isotopic tracers, but just through the inexistent concentrations of Cu, Bi and Mo found in the waters. In the proposed contamination model, climatic factors (glacial retreat) activate geological (ARD) processes. The tectonic scenario (faults) intervenes as a transport medium of the contamination flux from the sulphide oxidation surface in upper altitudes until the spring in lower altitudes. At the end, it is concluded that this contamination comes from the recent glacial retreat in areas near the Cordillera Blanca that has left massive amounts of sulphide materials exposed to weathering conditions, oxidizing naturally (ARD processes) and finally contributing to the contamination of the Negro River through faults. In this case, we would face an ARD process in the strict sense, which is the direct oxidation of sulphides outcropping in the upper part of the mountain with the generation of sulphates, the release of hydrogen ions and the consequent generation of acid and the dissolution of the metals. This ARD process would come from the glacial retreat, which, through the faults, transports contaminated water until the spring.

Application of fuzzy logic tools for the biogeochemical characterisation of (un)contaminated waters from Aljustrel mining area (South Portugal).

Aljustrel mining area (South Portugal) belongs to the Iberian Pyrite Belt (IPB). It is classified of high environmental risk due to its large tailings and to the Acid Mine Drainage (AMD) affected waters, generated by sulphides' oxidation. Integrating biological parameters (for the first time) in the input data matrix of the software PreFuRGe, allowed a better discrimination of the diatoms' responses to the stimuli caused by the hydrochemical changes imposed by the processes affecting water quality. Each hydrochemical scenario, was modeled by imposing maximum and minimum limits for each antecedent, according to the conditions imposed by the consequent, which in this case were the number of diatom species and pH. Thus, PreFuRGe evidenced some qualitative aspects that could not be achieved by classic statistics. pH appeared as the main discriminator of diversity and diatom species composition, nevertheless and due to the complex environment under study other chemical interactions must be considered: (a) AMD waters, with extremely low pH values, but also with extremely high hydrogeochemical complexity, represented by a mixture of metals, do not allow to associate, unequivocally, the reduction in diatom diversity to pH, but also to high metal (loid)s concentrations; (b) in the most alkaline waters, with higher abundance of diatom species, average to high concentrations of Na and Cl (due to Cenozoic sediments) do not seem to affect diatom diversity. This methodology proved to be an efficient tool to establish, for the first time, cause-effect relationships, improving the comprehension between biological (diatoms) and hydrochemical parameters.

Regulation of endothelial nitric oxide synthase expression in the vascular wall and in mononuclear cells from hypercholesterolemic rabbits.

BACKGROUND: We recently obtained evidence demonstrating that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3'-untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction. METHODS AND RESULTS: Endothelium-dependent relaxation to acetylcholine and the calcium ionophore A23187 was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg. kg body wt(-1). d(-1)) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the interaction of the cytosolic protein with the 3'-untranslated region of eNOS mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked reduction of eNOS expression and eNOS mRNA stability and an increase in binding activity of the cytosolic protein, which were also prevented by cerivastatin treatment. CONCLUSIONS: These results demonstrate the presence of a 60-kDa protein that binds to eNOS mRNA and reductions in eNOS expression in both vascular wall and mononuclear cells that are prevented by cerivastatin.

Doxazosin modifies Bcl-2 and Bax protein expression in the left ventricle of spontaneously hypertensive rats.

BACKGROUND: Increased apoptosis has recently been reported in the heart of spontaneously hypertensive rats (SHRs). OBJECTIVE: To investigate the molecular basis of apoptosis in the left ventricle of SHRs in terms of the expression of Bcl-2 protein (which protects from apoptosis) and Bax protein (which acts as an apoptotic promoter). In addition, we analysed the involvement of alpha -adrenergic receptors in the left ventricular apoptosis of SHRs. METHODS: The study was performed in untreated SHRs (n=16) and SHRs that were orally treated with doxazosin (10 mg/kg body weight per day, for 15 days), a selective alpha1-receptor blocker (n=16). A group of Wistar-Kyoto (WKY) rats (n=16) was used as the control. RESULTS: The left ventricles of untreated SHRs showed a significant increase in Bcl-2 protein expression and a reduced presence of Bax protein. The ratio of Bcl-2:Bax in SHRs was higher than in WKY rats, suggesting an anti-apoptotic state. Paradoxically, both the number of apoptotic cardiac cells and the cleavage of an 85-kDa fragment of the poly (ADP-ribose) polymerase (PARP), a marker of caspase-3 activity, were higher in the left ventricle of SHRs than in WKY rats, suggesting an apoptotic situation. Bax promotes cell apoptosis when it is bound to Bcl-2. We then determined the abundance of Bax-Bcl-2 complexes in the left ventricle of the two groups of animals. Bax-Bcl-2 complexes were more abundant in SHRs than WKY rats. In a second set of experiments, we analysed the role of alpha1-adrenergic blockade by doxazosin in the above-described mechanisms. Doxazosin treatment reduced the formation of Bax-Bcl-2 complexes in the left ventricle of SHRs, and this was accompanied by a decrease in the levels of 85kDa PARP and a reduction in apoptotic left ventricular cells. CONCLUSIONS: The present work suggests that the presence of Bax-Bcl-2 complexes in the left ventricle could be a more reliable marker of the apoptotic state than the determination of the absolute expression of Bcl-2 and Bax proteins. Moreover, the inhibition of alpha1 -adrenergic receptors by doxazosin decreased the abundance of BaxBcl-2 complexes and promoted a reduction of apoptosis in the left ventricle of SHRs.

Expression of inducible nitric oxide synthase in the liver of bile duct-ligated Wistar rats with modulation by lymphomononuclear cells.

BACKGROUND: The current study evaluated whether biliary tract obstruction stimulates inducible nitric oxide synthase (iNOS) protein expression in the liver and analyzed the implication of lymphomononuclear cells and interleukin-4 (IL-4). METHODS: Male Wistar rats were used. Bile flow interruption was achieved by a complete division of the extrapancreatic common bile duct. iNOS expression was determined by both the Western blot technique and immunohistochemistry. RESULTS: iNOS protein was markedly expressed in the liver 7 days after bile duct obstruction. Treatment with thymostimulin (TP-1), a partially purified thymic extract, reduced the intensity of the expression of iNOS protein in the liver after bile duct ligation. Recent data have suggested that IL-4 attenuates iNOS protein expression. We then analyzed the involvement of this anti-inflammatory cytokine on the modulation of iNOS expression in the liver. The liver from rats that underwent bile duct ligation (BDL) showed a lower content of IL-4 than that of sham-operated (SO) rats. TP-1 treatment increased the content of IL-4 in the liver. Liver slices incubated in vitro with Escherichia coli lipopolysaccharide (LPS, 10 microg/mL) stimulated the expression of iNOS protein. The level of LPS-induced iNOS expression was reduced by lymphomononuclear cells obtained from sham-operated animals. However, lymphomononuclear cells isolated from BDL rats potentiated the induction of iNOS expression by LPS-stimulated liver. However, lymphomononuclear cells from TP-1-treated BDL rats failed to modify LPS-stimulated iNOS expression. The different effect of lymphomononuclear cells on the modulation of iNOS expression in the liver was associated with their ability to generate IL-4. CONCLUSIONS: The liver of jaundiced rats markedly expressed iNOS protein, which was associated to modifications in the content of IL-4 in the liver. Furthermore, lymphomononuclear cells modulate iNOS protein expression in the liver by a mechanism in which IL-4 is involved.

Involvement of the liver by multiple myeloma as nodular lesions: a case diagnosed by fine-needle aspiration and immunocytochemistry.

Liver involvement by multiple myeloma as space-occupying lesions is a rare condition with only a few cases reported in the literature. We present a case of a 68-year-old man with a prostatic adenocarcinoma who developed a multiple myeloma as a second primary malignancy. Hepatic nodules were discovered in the tomographic study. Fine-needle aspiration of one of the hepatic lesions showed a pleomorphic plasmacytoid tumor. Immunocytochemistry using p63 and kappa-chain antibodies was useful in determining the plasmacytic nature of the cells.

A closed loop ML algorithm for phase aberration correction in phased array imaging systems. II. Performance analysis [Ultrasound medical imaging].

For pt.I see ibid., vol.44, pp.259-70 (1997). The performance of the maximum likelihood closed loop circuits, proposed in part I for phase aberration correction in phased array imaging systems, is analysed. This analysis is helpful in designing and also in determining the tracking mode phase error variance performance of both closed loop circuits (1-D and 2-D). It is an approximate analysis, suitable under small errors conditions, and considered accurate for high values of the signal to noise ratio.

A closed loop ML algorithm for phase aberration correction in phased array imaging systems. I. Algorithm synthesis and experimental results [Ultrasound medical imaging].

A new closed loop algorithm is described, based on the maximum likelihood theory, that corrects phase aberrations in phased array coherent imaging systems using phase estimates which are directly obtained from measured data (and not from estimated correlation functions). It has the advantage of estimating phase differences with respect to the same reference, and not phase differences between signals in adjacent array elements, eliminating the need to perform an integration to get the phase aberration profile. It allows for a real time implementation, in the sense that corrected data flows out of the circuit at the same rate that input data is fed into it. Being a closed loop algorithm, it is able to track time variations that may occur in the phase aberrations and, as in any phase lock loop circuit, it shows a trade-off between acquisition time and phase jitter.

[Doxazosin and soluble guanylate cyclase in a rat model of hypertension]. / Doxazosina y guanilato ciclasa soluble en un modelo de ratas hipertensas.

BACKGROUND: Although different studies have evaluated the ability of endothelial cells to produce NO in the setting of the endothelial dysfunction associated with hypertension, less it is known about the soluble guanylate cyclase system. AIM: To analyze the level of expression of sGC in the vascular wall in Stroke-prone spontaneously hypertensive rats (SHRSP). Moreover, the effect of treatment with an alpha1 adrenergic antagonist, doxazosin, on sGC expression was also evaluated. METHODS: The study was performed in 24 untreated 20-week-old SPSHR and 12 SPSHR treated orally with doxazosin (10 mg/Kg bw/day; for 15 days). A group of normotensive Wistar-Kyoto (WKY) rats were used as controls (n = 12). RESULTS: Isolated aortic segments from SHRSP showed impaired response to SNP. Doxazosin treatment prevented impaired vasodilatory response to SNP. Expression of the beta1 sGC in the vascular wall of SHRSP determined by Western blot and immunohistochemistry was markedly reduced with respect to that of WKY. Doxazosin treatment increased of beta1 sGC expression in treated SHRSP particularly at the medium level with respect to that of untreated SHRSP. CONCLUSION: SHRSP showed reduced expression of beta1 sGC in the vascular wall and an impaired vasodilator response to SNP which improved with doxazosin treatment. These results suggest the role the sGC system may play in the global treatment of endothelial dysfunction.

[Cancer of the middle third of the choledochus: an infrequent diagnosis]. / Cáncer de tercio medio de colédoco: un diagnóstico infrecuente.

We report the case of an 80-year-old woman with a previous history of HBP, hysterectomy due to cancer of the uterus and cholelithiasis, who was admitted in our hospital because of diffuse abdominal pain, marked jaundice, choluria and acholia during one week, together with anorexia and loss of weight. Blood chemistry results disclosed a total bilirubin of 11 mg/dl, a direct bilirubin of 8 mg/dl, GGTP 826 U/I, alkaline phosphatase 287 U/I, AST 285 U/I, ALT 837 U/I and LDH 242 U/I. The CA 19-9 marker was higher than 500 U/ml. The abdominal ultrasound examination did not show any space-occupying lesions; the extra and intrahepatic bile ducts were very dilated and the gall bladder showed multiple stones within its contents. The endoscopic retrograde cholangiopancreatography (ERCP) showed a homogeneous filiform defect at the middle third of the common bile duct of approximately 1 cm in length and with a marked dilatation of the bile ducts. A percutaneous drainage of the bile tree was performed, but the patient died.

Short-term effects of air pollution on respiratory morbidity at Rio de Janeiro--Part II: health assessment.

The effects of air pollution on health have been studied worldwide. Given that air pollution triggers oxidative stress and inflammation, it is plausible that high levels of air pollutants cause higher number of hospitalisations. This study aimed to assess the impact of air pollution on the emergency hospitalisation for respiratory disease in Rio de Janeiro, Brazil. The study was divided in two parts: Part I specifically addressing the air pollution assessment and Part II addressing the health assessment. Accordingly, this Part II aimed to estimate the association between the concentrations of PM10, SO2 and CO observed in Rio de Janeiro and the number of emergency hospitalisations at a central hospital due to respiratory diseases. The pollutant concentrations were measured at two different sites in Rio de Janeiro, but the excess relative risks were calculated based on the concentrations observed at one of the sites, where limits were generally exceeded more frequently, between September 2000 and December 2005. A time series analysis was performed using the number of hospitalisations, divided in three categories (children until 1 year old, children aged between 1 and 5 years old and elderly with 65 years old or more) as independent variable, the concentrations of pollutants as dependent variables and temperature, relative humidity, long term trend, and seasonality as confounders. Data were analysed using generalised additive models with smoothing for some of the dependent variables. Results showed an excess risk of hospitalisation for respiratory disease higher than 2% per 10 µg m⁻³ increase in PM10 concentrations for children under 5 years old, of 2% per 10 µg m⁻³ increase in SO2 for elderly above 65 years old and around 0.1% per 10 µg m⁻³ increase in CO for children under 1 year and elderly. Other studies have found associations that are in agreement with the results achieved in this study. The study suggests that the ambient levels of air pollutants experienced in Rio de Janeiro between 2000 and 2005 were linked to the number of hospitalisations for respiratory diseases among children and elderly.

Short-term effects of air pollution on respiratory morbidity at Rio de Janeiro--PART I: Air pollution assessment.

Exposure to air pollution has been related with the most varied adverse health outcomes. This study aims to assess the impact of air pollution on the emergency hospitalization for respiratory disease in Rio de Janeiro, Brazil. The study was divided in two parts: Part I specifically addressing the air pollution assessment and Part II addressing the health assessment. Accordingly, this Part I aims to: i) evaluate the concentrations of PM(10), SO(2) and CO at two sites in Rio de Janeiro and compare them; ii) analyse the concentrations observed according to the national and international standards; and iii) analyse the air pollutants behaviour, namely, annually, seasonally, daily and considering weekdays/weekends variations. The pollutant concentrations were measured at two different sites in Rio de Janeiro and the analysis was performed for the period between September 2000 and December 2005. Results showed that PM(10) concentrations in Rio de Janeiro exceeded the daily and annual standards imposed by the European Union, the Brazilian legislation and WHO guidelines. Regarding SO(2) and CO, concentrations were, generally, below both European and Brazilian standards. Nevertheless, considering WHO guidelines, SO(2) threshold for daily concentrations (20 µg m(-3)) was exceeded around 150 times. Behaviour assessment showed that the influence of traffic is a major factor affecting the air pollution in Rio de Janeiro. Considering the results achieved and the proven health effects of air pollution, strategies should be defined for its reduction, particularly concerning particulate matter, and consequently contribute to the protection of public health.